19-4207296-T-C

Variant names:

• chr19-4207296-T-C
• rs199801260
• NM_001393985.1:c.521T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001393985.1(ANKRD24):​c.521T>C​(p.Leu174Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00421 in 1,613,840 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (27 hom.)
• Consequence: ANKRD24 NM_001393985.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.02
• Publications: 8 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009562194).
• BP6: Variant 19-4207296-T-C is Benign according to our data. Variant chr19-4207296-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2649031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.521T>C	p.Leu174Pro	missense	Exon 8 of 22	NP_001380914.1	Q8TF21-1
	ANKRD24	NM_001393552.1		c.548T>C	p.Leu183Pro	missense	Exon 9 of 23	NP_001380481.1
	ANKRD24	NM_001393553.1		c.521T>C	p.Leu174Pro	missense	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.521T>C	p.Leu174Pro	missense	Exon 8 of 22	ENSP00000321731.4	Q8TF21-1
	ANKRD24	ENST00000597689.5	TSL:1	c.434T>C	p.Leu145Pro	missense	Exon 6 of 16	ENSP00000470227.1	M0QZ18
	ANKRD24	ENST00000262970.9	TSL:5	c.791T>C	p.Leu264Pro	missense	Exon 6 of 20	ENSP00000262970.4	Q8TF21-2

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 533 AN: 152046 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00314 AC: 782 AN: 249230 AF XY: 0.00319

Gnomad AFR exome AF: 0.000904

Gnomad AMR exome AF: 0.000696

Gnomad ASJ exome AF: 0.00686

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00223

Gnomad NFE exome AF: 0.00536

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00428 AC: 6259 AN: 1461676 Hom.: 27 Cov.: 32 AF XY: 0.00438 AC XY: 3185 AN XY: 727122

African (AFR) AF: 0.000627 AC: 21 AN: 33478

American (AMR) AF: 0.000715 AC: 32 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00719 AC: 188 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00285 AC: 152 AN: 53402

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00507 AC: 5633 AN: 1111844

Other (OTH) AF: 0.00373 AC: 225 AN: 60372

GnomAD4 genome AF: 0.00350 AC: 533 AN: 152164 Hom.: 2 Cov.: 31 AF XY: 0.00325 AC XY: 242 AN XY: 74408

African (AFR) AF: 0.000650 AC: 27 AN: 41520

American (AMR) AF: 0.00196 AC: 30 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00629 AC: 428 AN: 67996

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00487 Hom.: 1

Bravo AF: 0.00295

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.000755 AC: 3

ESP6500EA AF: 0.00420 AC: 35

ExAC AF: 0.00337 AC: 408

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00474

EpiControl AF: 0.00409

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
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.98	L
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.71
MVP		0.70
MPC		1.1
ClinPred		0.022	T
GERP RS		4.9
Varity_R		0.61
gMVP		0.56
Mutation Taster		=90/10	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: rs199801260; hg19: chr19-4207293; COSMIC: COSV53669939; COSMIC: COSV53669939;