NM_001372053.1:c.4918G>A

Variant names:

• chr5-75104641-C-T
• rs140882867
• NM_001372053.1:c.4918G>A

Variant summary

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

The NM_001372053.1(ANKRD31):​c.4918G>A​(p.Gly1640Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000778 in 1,535,960 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (7 hom.)
• Consequence: ANKRD31 NM_001372053.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.440
• Publications: 0 publications found

Genes affected

ANKRD31 (HGNC:26853): (ankyrin repeat domain 31) This gene encodes a protein containing multiple ankyrin repeats. Ankyrin domains function in protein-protein interactions in a variety of cellular processes. Mutations in this gene are associated with a Rett syndrome (RTT)-like phenotype. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004364431).
• BP6: Variant 5-75104641-C-T is Benign according to our data. Variant chr5-75104641-C-T is described in ClinVar as Benign. ClinVar VariationId is 791397.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372053.1. 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
	ANKRD31	NM_001372053.1	MANE Select	c.4918G>A	p.Gly1640Ser	missense	Exon 22 of 26	NP_001358982.1	D6RJB7
	ANKRD31	NM_001164443.1		c.4747G>A	p.Gly1583Ser	missense	Exon 21 of 25	NP_001157915.1	Q8N7Z5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD31	ENST00000506364.6	TSL:5 MANE Select	c.4918G>A	p.Gly1640Ser	missense	Exon 22 of 26	ENSP00000427262.2	D6RJB7
	ANKRD31	ENST00000274361.3	TSL:5	c.4747G>A	p.Gly1583Ser	missense	Exon 21 of 25	ENSP00000274361.3	Q8N7Z5
	ANKRD31	ENST00000504022.1	TSL:5	n.1708G>A		non_coding_transcript_exon	Exon 10 of 14

Frequencies

GnomAD3 genomes AF: 0.00385 AC: 586 AN: 152102 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00106 AC: 149 AN: 140694 AF XY: 0.000957

Gnomad AFR exome AF: 0.0142

Gnomad AMR exome AF: 0.000699

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000518

Gnomad OTH exome AF: 0.000240

GnomAD4 exome AF: 0.000438 AC: 606 AN: 1383740 Hom.: 7 Cov.: 32 AF XY: 0.000406 AC XY: 277 AN XY: 682708

African (AFR) AF: 0.0131 AC: 412 AN: 31490

American (AMR) AF: 0.000732 AC: 26 AN: 35508

Ashkenazi Jewish (ASJ) AF: 0.0000398 AC: 1 AN: 25154

East Asian (EAS) AF: 0.00109 AC: 39 AN: 35714

South Asian (SAS) AF: 0.000507 AC: 40 AN: 78898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34996

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5688

European-Non Finnish (NFE) AF: 0.0000213 AC: 23 AN: 1078440

Other (OTH) AF: 0.00107 AC: 62 AN: 57852

GnomAD4 genome AF: 0.00387 AC: 589 AN: 152220 Hom.: 1 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74438

African (AFR) AF: 0.0134 AC: 555 AN: 41540

American (AMR) AF: 0.000981 AC: 15 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00131 Hom.: 1

Bravo AF: 0.00420

ESP6500AA AF: 0.0137 AC: 19

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00148 AC: 30

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.44
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.022
Sift	Benign	0.090	T
Sift4G	Benign	0.20	T
Vest4		0.15
MVP		0.27
ClinPred		0.0040	T
GERP RS		2.9
Varity_R		0.040
gMVP		0.051
Mutation Taster		=99/1	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: rs140882867; hg19: chr5-74400466;