16-81042321-G-C

Position:

• chr16-81042321-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015251.3(ATMIN):​c.503G>C​(p.Ser168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATMIN NM_015251.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.685

Genes affected

ATMIN (HGNC:29034): (ATM interactor) Enables dynein complex binding activity. Involved in positive regulation of transcription, DNA-templated. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.08558804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATMIN	NM_015251.3	c.503G>C	p.Ser168Thr	missense_variant	3/4	ENST00000299575.5
ATMIN	NM_001300728.2	c.35G>C	p.Ser12Thr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATMIN	ENST00000299575.5	c.503G>C	p.Ser168Thr	missense_variant	3/4	1	NM_015251.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.503G>C (p.S168T) alteration is located in exon 3 (coding exon 3) of the ATMIN gene. This alteration results from a G to C substitution at nucleotide position 503, causing the serine (S) at amino acid position 168 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.69
DEOGEN2	Benign	0.056	T;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.72	T;.;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.086	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.82	L;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.14	N;.;.;N
REVEL	Benign	0.069
Sift	Benign	0.36	T;.;.;T
Sift4G	Benign	0.63	T;T;T;T
Polyphen		0.023	B;.;.;.
Vest4		0.25
MutPred		0.11		Loss of ubiquitination at K169 (P = 0.0477);.;.;.;
MVP		0.49
MPC		0.036
ClinPred		0.12	T
GERP RS		3.3
Varity_R		0.023
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-81075926;