11-134248810-C-G

Variant names:

• chr11-134248810-C-G
• NM_014174.3:c.630G>C

Variant summary

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

The NM_014174.3(THYN1):​c.630G>C​(p.Gln210His) variant causes a missense, splice region 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. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q210R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: THYN1 NM_014174.3 missense, splice_region
• Scores: Splicing: ADA: 0.0003868
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.903
• Publications: 0 publications found

Genes affected

THYN1 (HGNC:29560): (thymocyte nuclear protein 1) This gene encodes a protein that is highly conserved among vertebrates and plant species and may be involved in the induction of apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

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=0.18255368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THYN1	NM_014174.3	c.630G>C	p.Gln210His	missense_variant, splice_region_variant	Exon 6 of 7	ENST00000341541.8	NP_054893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THYN1	ENST00000341541.8	c.630G>C	p.Gln210His	missense_variant, splice_region_variant	Exon 6 of 7	1	NM_014174.3	ENSP00000341657.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.630G>C (p.Q210H) alteration is located in exon 6 (coding exon 6) of the THYN1 gene. This alteration results from a G to C substitution at nucleotide position 630, causing the glutamine (Q) at amino acid position 210 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;T;T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.2	M;M;M
PhyloP100		0.90
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.064	T;T;T
Sift4G	Benign	0.075	T;T;T
Polyphen		0.48	P;P;P
Vest4		0.35
MutPred		0.38		Loss of disorder (P = 0.1016);Loss of disorder (P = 0.1016);Loss of disorder (P = 0.1016);
MVP		0.13
MPC		0.33
ClinPred		0.58	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.16
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.024
SpliceAI score (max)		0.040		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

hg19: chr11-134118704;