5-75104425-G-C

Variant names:

• chr5-75104425-G-C
• rs768237186
• NM_001372053.1:c.5134C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001372053.1(ANKRD31):​c.5134C>G​(p.Leu1712Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000651 in 1,537,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1712F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: ANKRD31 NM_001372053.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06854668).

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.5134C>G	p.Leu1712Val	missense	Exon 22 of 26	NP_001358982.1	D6RJB7
	ANKRD31	NM_001164443.1		c.4963C>G	p.Leu1655Val	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.5134C>G	p.Leu1712Val	missense	Exon 22 of 26	ENSP00000427262.2	D6RJB7
	ANKRD31	ENST00000274361.3	TSL:5	c.4963C>G	p.Leu1655Val	missense	Exon 21 of 25	ENSP00000274361.3	Q8N7Z5
	ANKRD31	ENST00000504022.1	TSL:5	n.1924C>G		non_coding_transcript_exon	Exon 10 of 14

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000650 AC: 9 AN: 1384920 Hom.: 0 Cov.: 31 AF XY: 0.00000585 AC XY: 4 AN XY: 683384

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078878

Other (OTH) AF: 0.00 AC: 0 AN: 57912

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.9
DANN	Benign	0.85
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.83
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.042
Sift	Benign	0.15	T
Sift4G	Benign	0.23	T
Vest4		0.14
MutPred		0.22		Gain of sheet (P = 0.0028)
MVP		0.24
ClinPred		0.076	T
GERP RS		4.8
Varity_R		0.053
gMVP		0.020
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs768237186; hg19: chr5-74400250;