rs376848587

Variant names:

• chr19-4207242-C-T
• rs376848587
• NM_001393985.1:c.467C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001393985.1(ANKRD24):​c.467C>T​(p.Ala156Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense, splice_region
• Scores: Splicing: ADA: 0.0002254
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.777
• Publications: 1 publications found

Genes affected

ANKRD24 (HGNC:29424): (ankyrin repeat domain 24)

ANKRD24 Gene-Disease associations (from GenCC):

• sensorineural hearing loss disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000306086 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17511314).
• BP6: Variant 19-4207242-C-T is Benign according to our data. Variant chr19-4207242-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3394443.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393985.1. 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
	ANKRD24	NM_001393985.1	MANE Select	c.467C>T	p.Ala156Val	missense splice_region	Exon 8 of 22	NP_001380914.1	Q8TF21-1
	ANKRD24	NM_001393552.1		c.494C>T	p.Ala165Val	missense splice_region	Exon 9 of 23	NP_001380481.1
	ANKRD24	NM_001393553.1		c.467C>T	p.Ala156Val	missense splice_region	Exon 8 of 22	NP_001380482.1	Q8TF21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD24	ENST00000318934.9	TSL:5 MANE Select	c.467C>T	p.Ala156Val	missense splice_region	Exon 8 of 22	ENSP00000321731.4	Q8TF21-1
	ANKRD24	ENST00000597689.5	TSL:1	c.380C>T	p.Ala127Val	missense splice_region	Exon 6 of 16	ENSP00000470227.1	M0QZ18
	ANKRD24	ENST00000262970.9	TSL:5	c.737C>T	p.Ala246Val	missense splice_region	Exon 6 of 20	ENSP00000262970.4	Q8TF21-2

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151966 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000965 AC: 24 AN: 248790 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461492 Hom.: 0 Cov.: 32 AF XY: 0.0000715 AC XY: 52 AN XY: 727052

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000112 AC: 5 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000452 AC: 39 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111762

Other (OTH) AF: 0.0000663 AC: 4 AN: 60348

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152084 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6 AN XY: 74348

African (AFR) AF: 0.0000964 AC: 4 AN: 41496

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.0000910 AC: 11

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.78
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.28
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.010	B
Vest4		0.39
MVP		0.54
MPC		0.26
ClinPred		0.23	T
GERP RS		1.6
Varity_R		0.096
gMVP		0.18
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.090
SpliceAI score (max)		0.010		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: rs376848587; hg19: chr19-4207239; COSMIC: COSV99518389; COSMIC: COSV99518389;