rs149147457

Variant names:

• chr1-27547319-G-A
• rs149147457
• NM_001371928.1:c.4797C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001371928.1(AHDC1):​c.4797C>T​(p.Thr1599Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,544,876 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 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: AHDC1 NM_001371928.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.964
• Publications: 0 publications found

Genes affected

AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

AHDC1 Gene-Disease associations (from GenCC):

• AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)

ENSG00000300470 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-27547319-G-A is Benign according to our data. Variant chr1-27547319-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1232053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.964 with no splicing effect.
• BS2: High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371928.1. 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
	AHDC1	NM_001371928.1	MANE Select	c.4797C>T	p.Thr1599Thr	synonymous	Exon 8 of 9	NP_001358857.1	Q5TGY3
	AHDC1	NM_001029882.3		c.4797C>T	p.Thr1599Thr	synonymous	Exon 6 of 7	NP_001025053.1	Q5TGY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHDC1	ENST00000673934.1	MANE Select	c.4797C>T	p.Thr1599Thr	synonymous	Exon 8 of 9	ENSP00000501218.1	Q5TGY3
	AHDC1	ENST00000247087.10	TSL:5	c.4797C>T	p.Thr1599Thr	synonymous	Exon 5 of 6	ENSP00000247087.4	Q5TGY3
	AHDC1	ENST00000374011.6	TSL:5	c.4797C>T	p.Thr1599Thr	synonymous	Exon 6 of 7	ENSP00000363123.2	Q5TGY3

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000114 AC: 22 AN: 193338 AF XY: 0.000146

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000988

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000237 AC: 330 AN: 1392552 Hom.: 0 Cov.: 30 AF XY: 0.000221 AC XY: 152 AN XY: 686840

African (AFR) AF: 0.0000646 AC: 2 AN: 30966

American (AMR) AF: 0.00 AC: 0 AN: 32654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21294

East Asian (EAS) AF: 0.00 AC: 0 AN: 39186

South Asian (SAS) AF: 0.000306 AC: 23 AN: 75086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5414

European-Non Finnish (NFE) AF: 0.000253 AC: 273 AN: 1080628

Other (OTH) AF: 0.000559 AC: 32 AN: 57262

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74476

African (AFR) AF: 0.0000722 AC: 3 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000335 Hom.: 0

Bravo AF: 0.000162

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs149147457; hg19: chr1-27873830;