rs1024112369

Variant names:

• chr17-76710881-G-A
• rs1024112369
• NM_198530.4:c.66C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_198530.4(MXRA7):​c.66C>T​(p.Leu22Leu) 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 146,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MXRA7 NM_198530.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• Publications: 0 publications found

Genes affected

MXRA7 (HGNC:7541): (matrix remodeling associated 7) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SNHG16 (HGNC:44352): (small nucleolar RNA host gene 16)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-76710881-G-A is Benign according to our data. Variant chr17-76710881-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3778193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.53 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198530.4. 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
	MXRA7	NM_198530.4	MANE Select	c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 4	NP_940932.2
	MXRA7	NM_001008528.3		c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 4	NP_001008528.1	P84157-1
	MXRA7	NM_001008529.3		c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 5	NP_001008529.1	P84157-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MXRA7	ENST00000449428.7	TSL:1 MANE Select	c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 4	ENSP00000391466.1	P84157-2
	MXRA7	ENST00000355797.7	TSL:2	c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 4	ENSP00000348050.2	P84157-1
	MXRA7	ENST00000375036.6	TSL:2	c.66C>T	p.Leu22Leu	synonymous	Exon 1 of 5	ENSP00000364176.1	P84157-3

Frequencies

GnomAD3 genomes AF: 0.000219 AC: 32 AN: 146266 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000678

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000410

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000303 AC: 257 AN: 848262 Hom.: 0 Cov.: 23 AF XY: 0.000306 AC XY: 121 AN XY: 396034

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000633 AC: 1 AN: 15792

American (AMR) AF: 0.00 AC: 0 AN: 1502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5584

East Asian (EAS) AF: 0.00 AC: 0 AN: 4058

South Asian (SAS) AF: 0.00 AC: 0 AN: 18626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1692

European-Non Finnish (NFE) AF: 0.000325 AC: 251 AN: 772358

Other (OTH) AF: 0.000180 AC: 5 AN: 27818

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000232 AC: 34 AN: 146374 Hom.: 0 Cov.: 29 AF XY: 0.000154 AC XY: 11 AN XY: 71270

African (AFR) AF: 0.000122 AC: 5 AN: 40936

American (AMR) AF: 0.0000677 AC: 1 AN: 14774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8344

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000410 AC: 27 AN: 65794

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.000169 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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	-0.50
CADD	Benign	9.4
DANN	Uncertain	0.98
PhyloP100		-1.5
PromoterAI		0.039	Neutral

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: rs1024112369; hg19: chr17-74706963;