chr10-72097364-G-A

Variant names:

• chr10-72097364-G-A
• rs146138639
• NM_001198800.3:c.1044C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001198800.3(ASCC1):​c.1044C>T​(p.Tyr348Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,613,400 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (2 hom.)
• Consequence: ASCC1 NM_001198800.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 0 publications found

Genes affected

ASCC1 (HGNC:24268): (activating signal cointegrator 1 complex subunit 1) This gene encodes a subunit of the activating signal cointegrator 1 (ASC-1) complex. The ASC-1 complex is a transcriptional coactivator that plays an important role in gene transactivation by multiple transcription factors including activating protein 1 (AP-1), nuclear factor kappa-B (NF-kB) and serum response factor (SRF). The encoded protein contains an N-terminal KH-type RNA-binding motif which is required for AP-1 transactivation by the ASC-1 complex. Mutations in this gene are associated with Barrett esophagus and esophageal adenocarcinoma. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ASCC1 Gene-Disease associations (from GenCC):

• spinal muscular atrophy with congenital bone fractures 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 10-72097364-G-A is Benign according to our data. Variant chr10-72097364-G-A is described in ClinVar as Benign. ClinVar VariationId is 720317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.41 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000972 (148/152332) while in subpopulation AFR AF = 0.0031 (129/41572). AF 95% confidence interval is 0.00267. There are 0 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198800.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	NM_001198800.3	MANE Select	c.1044C>T	p.Tyr348Tyr	synonymous	Exon 10 of 10	NP_001185729.1	Q8N9N2-2
	ASCC1	NM_001198798.2		c.1044C>T	p.Tyr348Tyr	synonymous	Exon 10 of 10	NP_001185727.1	Q8N9N2-2
	ASCC1	NM_001369093.1		c.1044C>T	p.Tyr348Tyr	synonymous	Exon 10 of 10	NP_001356022.1	Q8N9N2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCC1	ENST00000672957.1	MANE Select	c.1044C>T	p.Tyr348Tyr	synonymous	Exon 10 of 10	ENSP00000500935.1	Q8N9N2-2
	ASCC1	ENST00000902262.1		c.1128C>T	p.Tyr376Tyr	synonymous	Exon 11 of 11	ENSP00000572321.1
	ASCC1	ENST00000672774.1		c.1104C>T	p.Tyr368Tyr	synonymous	Exon 11 of 11	ENSP00000500488.1	A0A5F9ZHP1

Frequencies

GnomAD3 genomes AF: 0.000939 AC: 143 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000421 AC: 106 AN: 251486 AF XY: 0.000405

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000155 AC: 226 AN: 1461068 Hom.: 2 Cov.: 30 AF XY: 0.000144 AC XY: 105 AN XY: 726866

African (AFR) AF: 0.00371 AC: 124 AN: 33460

American (AMR) AF: 0.000403 AC: 18 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.000731 AC: 29 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111360

Other (OTH) AF: 0.000298 AC: 18 AN: 60332

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000792 AC XY: 59 AN XY: 74482

African (AFR) AF: 0.00310 AC: 129 AN: 41572

American (AMR) AF: 0.000523 AC: 8 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000817 Hom.: 0

Bravo AF: 0.00120

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.4
DANN	Benign	0.46
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146138639; hg19: chr10-73857122; COSMIC: COSV100403315;