6-97149956-C-T

Variant names:

• chr6-97149956-C-T
• rs764681347
• NM_001350599.2:c.3547G>A

Variant summary

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

The NM_001350599.2(MMS22L):​c.3547G>A​(p.Ala1183Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MMS22L NM_001350599.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350599.2. 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
	MMS22L	NM_001350599.2	MANE Select	c.3547G>A	p.Ala1183Thr	missense	Exon 24 of 25	NP_001337528.1	Q6ZRQ5
	MMS22L	NM_198468.4		c.3547G>A	p.Ala1183Thr	missense	Exon 24 of 25	NP_940870.2	Q6ZRQ5
	MMS22L	NM_001350600.2		c.2698G>A	p.Ala900Thr	missense	Exon 23 of 24	NP_001337529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS22L	ENST00000683635.1	MANE Select	c.3547G>A	p.Ala1183Thr	missense	Exon 24 of 25	ENSP00000508046.1	Q6ZRQ5
	MMS22L	ENST00000275053.8	TSL:2	c.3547G>A	p.Ala1183Thr	missense	Exon 24 of 25	ENSP00000275053.4	Q6ZRQ5
	MMS22L	ENST00000929352.1		c.3547G>A	p.Ala1183Thr	missense	Exon 24 of 25	ENSP00000599411.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152040 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: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251078 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461436 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727012

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111724

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15248

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.18
BayesDel_addAF	Benign	0.0059	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.22
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.37		Loss of helix (P = 0.0304)
MVP		0.16
MPC		0.36
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.11
gMVP		0.50
Mutation Taster		=87/13	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: rs764681347; hg19: chr6-97597832;