dbSNP rs373483639: MMS22L:p.Ser1195Ala (chr6-97149920-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001350599.2(MMS22L):c.3583T>G(p.Ser1195Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. S1195T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MMS22L
NM_001350599.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.918

Variant links:

Genes affected

MMS22L (HGNC:21475): (MMS22 like, DNA repair protein) The protein encoded by this gene forms a complex with tonsoku-like, DNA repair protein (TONSL), and this complex recognizes and repairs DNA double-strand breaks at sites of stalled or collapsed replication forks. The encoded protein also can bind with the histone-associated protein NFKBIL2 to help regulate the chromatin state at stalled replication forks. Finally, this gene appears to be overexpressed in most lung and esophageal cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MMS22L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1439381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS22L	NM_001350599.2 link	c.3583T>G	p.Ser1195Ala	missense_variant	Exon 24 of 25	ENST00000683635.1	NP_001337528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMS22L	ENST00000683635.1 link	c.3583T>G	p.Ser1195Ala	missense_variant	Exon 24 of 25		NM_001350599.2	ENSP00000508046.1	Q6ZRQ5
MMS22L	ENST00000275053.8 link	c.3583T>G	p.Ser1195Ala	missense_variant	Exon 24 of 25	2		ENSP00000275053.4	Q6ZRQ5
MMS22L	ENST00000369251.6 link	c.3463T>G	p.Ser1155Ala	missense_variant	Exon 22 of 23	2		ENSP00000358254.2	E2QRD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.065

Sift

Benign

0.034

D;D

Sift4G

Benign

0.062

T;T

Polyphen

0.17

B;B

Vest4

0.33

MutPred

0.56

Gain of helix (P = 0.027);.;

MVP

0.068

MPC

0.065

ClinPred

0.55

GERP RS

-1.3

Varity_R

0.11

gMVP

0.17

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over